Cancer Science最新文献

{"title":"In Vitro Expansion and Transduction of Primary NK Cells Using Feeder Cells Expressing Costimulatory Molecules and IL-21.","authors":"Thi Bao Tram Tran, Thi Van Anh Bui, Thi Minh Thu Tran, Nguyen Minh Nguyen, Hoang Thien Phuc Nguyen, Thi Phuong Diem Tran, Duc Minh Quan Nguyen, Thai Minh Quan Ngo, Thanh Binh Nguyen, Els Verhoeyen, Nhat Thang Tran, Hoai-Nghia Nguyen, Le Son Tran","doi":"10.1111/cas.70090","DOIUrl":"https://doi.org/10.1111/cas.70090","url":null,"abstract":"<p><p>Natural Killer (NK) cells are an important population of the immune system, and NK cell-based therapy has shown great potential in the treatment of cancers. However, to apply NK cells clinically, producing a large number of cells with high cytotoxicity remains a challenge. Current strategies focus on employing different irradiated feeder cells to stimulate NK expansion, maturation, and cytotoxicity. While co-stimulatory signals play critical roles in promoting NK cell proliferation and activating their functions, the exploitation of these signals for expanding NK cells has not been fully explored. To identify the optimal engineered feeder cells for expanding umbilical cord blood-derived NK cells, we generated different feeder cells expressing the co-stimulatory molecules CD80, 4-1BBL, or membrane-bound IL-21 (mbIL21). We then evaluated the transduction efficacy of a chimeric antigen receptor (CAR) construct into expanded NK cells using various lentiviral vectors. Our results showed that CD80, in combination with 4-1BBL and mbIL21, induced the highest expansion of NK cells from cord blood. The expanded NK cells displayed higher cytotoxicity toward target cells compared to T cells following CAR transduction using BaEV lentivirus.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the RAB27/SYTL Axis in Tumor Microenvironment Construction.","authors":"Miwa Tanaka, Takuro Nakamura","doi":"10.1111/cas.70096","DOIUrl":"https://doi.org/10.1111/cas.70096","url":null,"abstract":"<p><p>Crosstalk between cancer cells and the tumor microenvironment (TME) is a key event in malignant progression and metastasis. The secretion of bioactive substances by cancer cells remodels the TME, affecting the activities of its components, including blood vessels, mesenchymal cells, and immune cells. These substances are effectively delivered through intracellular trafficking and exocytosis of cytoplasmic vesicles. The small guanosine triphosphatase (GTPase) RAB27 and its effectors, synaptotagmin-like (SYTL) family proteins, play essential roles in vesicle trafficking. Our recent research demonstrates the upregulation of RAB27A/B and SYTL1/2 in alveolar soft part sarcoma and acute myeloid leukemia. This enhanced trafficking promotes angiogenesis and the occupation of leukemia cells in the bone marrow niche. This review focuses on the role of the RAB27/SYTL axis in various cancer types associated with TME modifications, with a discussion on its importance as a therapeutic target.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polo-Like Kinase 1 Expression in Colorectal Cancer: Association With RAS Mutations.","authors":"Yasushi Tanaka, Eiji Oki, Ryota Nakanishi, Tetsuro Kawazoe, Kensuke Kudo, Yoko Zaitsu, Yuichi Hisamatsu, Koji Ando, Yoshinao Oda, Tomoharu Yoshizumi","doi":"10.1111/cas.70088","DOIUrl":"https://doi.org/10.1111/cas.70088","url":null,"abstract":"<p><p>Polo-like kinase 1 (PLK1) controls mitotic spindle formation and cytokinesis. However, its role as a predictive biomarker for treatment outcomes in colorectal cancer (CRC) remains underexplored, particularly in the context of RAS mutations. We retrospectively analyzed the relationships among PLK1 expression, clinicopathological factors, and survival in 225 patients who underwent CRC surgery. We also analyzed the relationship between PLK1 expression and survival after adjuvant chemotherapy and how RAS mutation influenced the prognosis. We found that PLK1 expression was significantly correlated with histopathology (p < 0.0001) and perineural invasion (p = 0.005). The high PLK1 expression group tended to have a worse prognosis in terms of relapse-free survival than the low expression group for all patients (p = 0.060) and patients with stage III disease (p = 0.055). In patients who received adjuvant chemotherapy for stage III CRC, high PLK1 expression was the only poor prognostic factor for relapse-free survival (p = 0.01), and those with mutated RAS had a significantly poorer prognosis than those with wild-type RAS (p = 0.027). In patients with CRC, high PLK1 expression was associated with poor survival after adjuvant chemotherapy, and there was potential involvement of the RAS mutation.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-Type-Specific DNA Methylation Is a Source of Vulnerability in Liver Cancer Cells.","authors":"Karen Minowa, Miho Seki, Yui Nagai, Satoshi Yamashita","doi":"10.1111/cas.70092","DOIUrl":"https://doi.org/10.1111/cas.70092","url":null,"abstract":"<p><p>DNA methylation, a pivotal epigenetic mechanism, plays a critical role in various pathological conditions, including cancers. Notably, cancer-type-specific DNA methylation can be advantageous for survival only in specific environments while being disadvantageous in others. To investigate the role of cancer-type-specific methylation as a vulnerability in cancer cells, we bioinformatically profiled genome-wide DNA methylation in 1165 human cancer cell lines across 25 cancer types. The number of cancer-type-specific methylated cytosines varied significantly by organ, with exceptionally high numbers observed in blood cancers. A total of 73 genes were identified as potential liver cancer-specific methylation-silenced genes, and four genes, ASNS, NQO1, FXYD5, and BCAT2, were subjected to experimental further analysis. Silencing of BCAT2 was found to contribute to the vulnerability of liver cancer cells to BCAT1 inhibition by gabapentin. Additionally, the silencing of the other three genes also rendered liver cancer cells vulnerable under different environmental conditions. These findings enhance our understanding of the biological and clinical significance of DNA methylation and provide a basis for developing diagnostic markers for cancer. (169 words).</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: miR-25-3p Reverses Epithelial-Mesenchymal Transition via Targeting Sema4C in Cisplatin-Resistance Cervical Cancer Cells.","authors":"","doi":"10.1111/cas.70083","DOIUrl":"https://doi.org/10.1111/cas.70083","url":null,"abstract":"<p><strong>Retraction: </strong>J. Song and Y. Li, \"miR-25-3p Reverses Epithelial-Mesenchymal Transition via Targeting Sema4C in Cisplatin-Resistance Cervical Cancer Cells,\" Cancer Science 108, no. 1 (2017): 23-31, https://doi.org/10.1111/cas.13104. The above article, published online on 01 December 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Masanori Hatakeyama; the Japanese Cancer Association; and John Wiley & Sons Australia Ltd. The retraction has been agreed following an investigation into concerns raised by a third party, which revealed inappropriate duplication of image panels (Figures 1b, 2a, b and 3c) between this and several other articles published previously or in the same year by a different group of authors, in a different scientific context. Given the extent of the identified issues, the editors have lost confidence in the data presented and the article's conclusions can no longer be considered reliable. The authors and their institute have been informed of the concerns and the decision to retract but they remained unresponsive.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Contrast-Enhanced Ultrasound Cine-Based Deep Learning Model for Predicting the Response of Advanced Hepatocellular Carcinoma to Hepatic Arterial Infusion Chemotherapy Combined With Systemic Therapies.","authors":"Xu Han, Chuan Peng, Si-Min Ruan, Lingling Li, Minke He, Ming Shi, Bin Huang, Yudi Luo, Jingming Liu, Huiying Wen, Wei Wang, Jianhua Zhou, Minhua Lu, Xin Chen, Ruhai Zou, Zhong Liu","doi":"10.1111/cas.70089","DOIUrl":"https://doi.org/10.1111/cas.70089","url":null,"abstract":"<p><p>Recently, a hepatic arterial infusion chemotherapy (HAIC)-associated combination therapeutic regimen, comprising HAIC and systemic therapies (molecular targeted therapy plus immunotherapy), referred to as HAIC combination therapy, has demonstrated promising anticancer effects. Identifying individuals who may potentially benefit from HAIC combination therapy could contribute to improved treatment decision-making for patients with advanced hepatocellular carcinoma (HCC). This dual-center study was a retrospective analysis of prospectively collected data with advanced HCC patients who underwent HAIC combination therapy and pretreatment contrast-enhanced ultrasound (CEUS) evaluations from March 2019 to March 2023. Two deep learning models, AE-3DNet and 3DNet, along with a time-intensity curve-based model, were developed for predicting therapeutic responses from pretreatment CEUS cine images. Diagnostic metrics, including the area under the receiver-operating-characteristic curve (AUC), were calculated to compare the performance of the models. Survival analysis was used to assess the relationship between predicted responses and prognostic outcomes. The model of AE-3DNet was constructed on the top of 3DNet, with innovative incorporation of spatiotemporal attention modules to enhance the capacity for dynamic feature extraction. 326 patients were included, 243 of whom formed the internal validation cohort, which was utilized for model development and fivefold cross-validation, while the rest formed the external validation cohort. Objective response (OR) or non-objective response (non-OR) were observed in 63% (206/326) and 37% (120/326) of the participants, respectively. Among the three efficacy prediction models assessed, AE-3DNet performed superiorly with AUC values of 0.84 and 0.85 in the internal and external validation cohorts, respectively. AE-3DNet's predicted response survival curves closely resembled actual clinical outcomes. The deep learning model of AE-3DNet developed based on pretreatment CEUS cine performed satisfactorily in predicting the responses of advanced HCC to HAIC combination therapy, which may serve as a promising tool for guiding combined therapy and individualized treatment strategies. Trial Registration: NCT02973685.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The C11orf24 Gene as a Useful Biomarker for Predicting Severe Neutropenia in Modified FOLFIRINOX for Pancreatic Cancer.","authors":"Gen Kanesada, Ryouichi Tsunedomi, Yuki Nakagami, Hiroto Matsui, Yoshitaro Shindo, Shinobu Tomochika, Hirofumi Akita, Tatsuya Ioka, Hidenori Takahashi, Hiroaki Nagano","doi":"10.1111/cas.70087","DOIUrl":"https://doi.org/10.1111/cas.70087","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is an aggressive and lethal tumor with a poor prognosis. FOLFIRINOX improves the prognosis of patients with PC; however, despite UGT1A1 screening, adverse events, such as severe neutropenia, occur frequently. This study aimed to identify the novel biomarkers of severe neutropenia in patients treated with modified FOLFIRINOX (mFFX) for PC. In this study, patients with PC treated with mFFX (n = 71) and gemcitabine plus nab-paclitaxel (GnP) (n = 92) and patients with colorectal cancer treated with FOLFOXIRI (n = 50) were included. Genome-wide screening using whole-exome sequencing was performed during the screening phase. Validation analysis was performed using polymerase chain reaction genotyping, the Cochran-Armitage trend test, and multivariate analysis. The diagnostic performance of combined risk factors for severe neutropenia was examined using logistic regression with leave-one-out cross-validation. Three gene polymorphisms were selected from the screening phase and subjected to the validation phase. In the validation phase, a single nucleotide polymorphism in C11orf24 (c.448C>T, rs901827) was significantly correlated with ≥ Grade 3 neutropenia in mFFX and FOLFOXIRI but not in GnP. Multivariate analysis showed C11orf24 and baseline neutrophil count as independent risk factors for ≥ Grade 3 neutropenia. The diagnostic performance of the neutropenia prediction model showed areas under the curve of 0.754 (sensitivity = 0.605, specificity = 0.848) and 0.856 (sensitivity = 0.800, specificity = 0.893) for ≥ Grade 3 and 4 neutropenia, respectively. The C11orf24 gene and baseline neutrophil count may be useful biomarkers for predicting severe neutropenia following irinotecan-containing triplet chemotherapy.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDX2 Promoter-Controlled Oncolytic Adenovirus Suppresses Tumor Growth and Liver Metastasis of Colorectal Cancer.","authors":"Naohiko Nakamura, Mizuho Sato-Dahlman, Elise Travis, Kari Jacobsen, Masato Yamamoto","doi":"10.1111/cas.70063","DOIUrl":"https://doi.org/10.1111/cas.70063","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and liver metastasis (CRLM) is the most common among its distant metastases. We have recently generated a CDX2 promoter-controlled oncolytic adenovirus (Ad5/3-pCDX2) that showed an anticancer effect for CDX2-positive upper gastrointestinal tumors. Here, we reported the anticancer effect of Ad5/3-pCDX2 for CDX2-positive CRC and CRLM, and its combination efficacy with 5-fluorouracil (5FU) in vitro and in vivo. We used HT29 as CDX2-positive, and LS174T and SW480 as CDX2-negative CRC cell lines. Without 5FU, Ad5/3-pCDX2 killed HT29 but not LS174T and SW480 cells. In vitro, 5FU exposure upregulated CDX2 mRNA levels in all three cell lines. The 5FU combination enhanced the cytocidal effect and virus replication of Ad5/3-pCDX2 in CDX2-negative LS174T. In mouse xenograft models, Ad5/3-pCDX2 monotherapy suppressed the HT29 subcutaneous tumor growth compared to the control group. The 5FU plus Ad5/3-pCDX2 combination therapy showed a remarkable antitumor effect over the efficacy of Ad5/3-pCDX2 monotherapy. In the LS174T subcutaneous tumor, although Ad5/3-pCDX2 monotherapy did not show an antitumor effect, the 5FU plus Ad5/3-pCDX2 combination therapy significantly suppressed the tumor growth compared to the Ad5/3-pCDX2 monotherapy. In mice with HT29 liver metastasis, intrasplenic injection of Ad5/3-pCDX2 induced virus replication in liver tumors and thus successfully attenuated tumor growth. In conclusion, Ad5/3-pCDX2 showed a significant anticancer effect that was enhanced by 5FU treatment in not only CDX2-positive but also negative CRCs. Ad5/3-pCDX2 is a promising therapeutic modality for metastatic CRC such as CRLM.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrotinib and Nab-Paclitaxel in HER2-Positive Breast Cancer (PANHER Trial): A Prospective, Single-Arm, Phase II Trial.","authors":"Huan Li, Min Yan, Zhaohui Li, Xiujie Cui, Xuening Ji, Fengqi Fang, Yuyang Zhang, Yan Wang, Xiangyu Guo, Mingxi Jing, Zhichao Gao, Hui Cao, Fangyuan Dong, Jie Wu, Cui Jiang, Yangyang Duan, Xiaorui Li, Yujun Jiang, Lei Jiang, Ying E, Yufeng Jia, Liang Zhang, Pai Peng, Tao Sun","doi":"10.1111/cas.70086","DOIUrl":"https://doi.org/10.1111/cas.70086","url":null,"abstract":"<p><p>Trastuzumab and pertuzumab combined with chemotherapy represent the standard therapy for first-line treatment of HER2-positive metastatic breast cancer (BC). Due to challenges related to availability and cost in China, it is necessary to explore treatments involving tyrosine kinase inhibitors (TKIs). In this multicenter, single-arm, open-label phase II trial, patients with HER2-positive BC were enrolled from seven hospitals in China. Patients received oral pyrotinib 400 mg once daily and intravenous nab-paclitaxel 125 mg/m² on days 1, 8, and 15 of each 28-day cycle until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). Between December 2019 and December 2021, 51 patients were enrolled. Among all enrolled patients, 48 had at least one response evaluation. Of these evaluable patients, 39 patients achieved responses, resulting in a positive study outcome. The ORR was 76.5% (95% CI, 62.5%-87.2%), and the disease control rate was 94.1% (95% CI, 83.8-98.8). As of January 24, 2024, the median follow-up duration was 29.2 months (IQR, 24.9-33.2). The median progression-free survival was 14.6 months (95% CI, 8.0-24.2), and the median overall survival was not reached. Forty-nine patients (96.1%) developed grade ≥ 3 adverse events (AEs). The most common grade ≥ 3 AEs were decreased neutrophil count (43.1%), decreased white blood cell count (43.1%), and diarrhea (23.5%). Pyrotinib combined with nab-paclitaxel demonstrated promising efficacy for HER2-positive advanced breast cancer, with an acceptable safety profile. Trial Registration: chictr.org, ChiCTR1900023653.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vivo Reprogramming Highlights Epigenetic Regulation That Shapes Cancer Hallmarks.","authors":"Yosuke Yamada, Nao Sankoda, Yasuhiro Yamada","doi":"10.1111/cas.70067","DOIUrl":"https://doi.org/10.1111/cas.70067","url":null,"abstract":"<p><p>Douglas Hanahan added \"non-mutational epigenetic reprogramming\" and \"unlocking phenotypic plasticity\" as new hallmarks of cancer, proposing that cancer cells possess fundamental features that are not directly linked to their genetic abnormalities. In vivo reprogramming studies have demonstrated that non-mutational epigenetic regulation can cause cellular reprogramming, leading to cancer development at the organismal level. Given that epigenetic regulation functions as an interface between the cellular environment and gene expression, these results suggest that intercellular communications in the tumor microenvironment play a critical role in cancer development. This review first introduces genetic aberrations that cause cancer development. Then, it illustrates the impact of epigenetic abnormalities in cancer, especially with reference to studies that use in vivo reprogramming technologies. Finally, it discusses the importance of histological evaluations of tumor tissue to understand non-cell-autonomous epigenetic regulation that establishes cancer hallmarks.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}